Long, Noncoding RNA Dysregulation in Glioblastoma

Abstract

Transcription occurs across more than 70% of the human genome and more than half of currently annotated genes produce functional noncoding RNAs. Of these transcripts, the majority—long, noncoding RNAs (lncRNAs)—are greater than 200 nucleotides in length and are necessary for various roles in the cell. It is increasingly appreciated that these lncRNAs are relevant in both health and disease states, with the brain expressing the largest number of lncRNAs compared to other organs. Glioblastoma (GBM) is an aggressive, fatal brain tumor that demonstrates remarkable intratumoral heterogeneity, which has made the development of effective therapies challenging. The cooperation between genetic and epigenetic alterations drives rapid adaptation that allows therapeutic evasion and recurrence. Given the large repertoire of lncRNAs in normal brain tissue and the well-described roles of lncRNAs in molecular and cellular processes, these transcripts are important to consider in the context of GBM heterogeneity and treatment resistance. Herein, we review the general mechanisms and biological roles of lncRNAs, with a focus on GBM, as well as RNA-based therapeutics currently in development.

Prognostic utility of lncRNAs (LINC00565 and LINC00641) as molecular markers in glioblastoma multiforme (GBM)

“…Given the sizable studies of the role for lncRNAs cellular processes [ 34 , 36 ] made them important to be considered in the context of GBM heterogeneity and treatment resistance. In the current study the median follow-up for GBM patients was 10 months and the estimated median PFS was 11 months and median OS was 13 months which concurrent with the median follow up period of previous studies on GBM [ 37 , 38 ].…”

Prognostic Utility of LncRNAs (LINC00565 and LINC00641) as Molecular Markers in Glioblastoma Multiforme (GBM)

“…Given the sizable studies of the role for lncRNAs cellular processes 31,29 made them important to be considered in the context of GBM heterogeneity and treatment resistance.…”

Post-Transcriptional Modifications of RNA as Regulators of Apoptosis in Glioblastoma

“…The functional versatility of lncRNAs is related to their ability to conform to various structures and molecular interactions with DNA, RNA and proteins [ 64 ]. The relationship of lncRNAs to the development of glioblastoma has already been described in a number of reviews [ 65 , 66 , 67 ] and studied in meta-analyses [ 68 , 69 ], which have already identified potential targets for developing diagnosis, prognosis assessment, and combination therapy. LncRNAs can indirectly affect the post-translational modifications of RNA, and hence can affect processes of oncogenesis such as apoptosis.…”